A Rab3a-dependent complex essential for lysosome positioning and plasma membrane repair

Marisa Encarnação, Lília Espada, Cristina Escrevente, Denisa Mateus, José Ramalho, Xavier Michelet, Inês Santarino, Victor W Hsu, Michael B Brenner, Duarte Barral, Otília V Vieira

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Lysosome exocytosis plays a major role in resealing plasma membrane (PM) disruptions. This process involves two sequential steps. First, lysosomes are recruited to the periphery of the cell and then fuse with the damaged PM. However, the trafficking molecular machinery involved in lysosome exocytosis and PM repair (PMR) is poorly understood. We performed a systematic screen of the human Rab family to identify Rabs required for lysosome exocytosis and PMR. Rab3a, which partially localizes to peripheral lysosomes, was one of the most robust hits. Silencing of Rab3a or its effector, synaptotagmin-like protein 4a (Slp4-a), leads to the collapse of lysosomes to the perinuclear region and inhibition of PMR. Importantly, we have also identified a new Rab3 effector, nonmuscle myosin heavy chain IIA, as part of the complex formed by Rab3a and Slp4-a that is responsible for lysosome positioning at the cell periphery and lysosome exocytosis.

Original languageEnglish
Pages (from-to)631-40
Number of pages10
JournalJournal Of Cell Biology
Volume213
Issue number6
DOIs
Publication statusPublished - 20 Jun 2016

Keywords

  • ARF-LIKE GTPASE
  • MYCOBACTERIUM-TUBERCULOSIS
  • EXOCYTOSIS
  • CELLS
  • SYNAPTOTAGMIN
  • DISRUPTION
  • VESICLES
  • RAB3A; FIBROBLASTS
  • MECHANISM

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